Composition, method and kit for enhancing hair

ABSTRACT

Compositions for application and methods of application of a composition to modify hair. In one embodiment, a composition includes a compound (molecule) represented by: 
     
       
         
         
             
             
         
       
         
         
           
             wherein A and B are individually selected from a hydrogen, a hydroxyl group and a halogen, with the proviso that when one of A and B is a hydroxyl group, the other of A and B is a hydrogen and when one of A and B is a halogen, the other of A and B is a halogen or a hydrogen; 
             wherein Z is, for example, an aryl moiety; and 
             wherein X 1  and X 2  are, for example, individually selected from a hydrogen and an alkyl moiety, 
             wherein R 1  and R 2  are individually selected from an oxo, a hydroxyl or an ester group; 
             wherein y is 0 or 1, x is 0 or 1 and x and y are not both 1, or a salt.

CROSS-REFERENCE TO RELATED APPLICATION

The application is a divisional application of co-pending U.S. patentapplication Ser. No. 13/631,193, filed Sep. 28, 2012, which is acontinuation of co-pending U.S. patent application Ser. No. 12/698,823,filed Feb. 2, 2010, which claims the benefit of the earlier filing dateof co-pending U.S. Provisional Patent Application No. 61/149,661, filedFeb. 3, 2009 and incorporated herein by reference.

FIELD

Composition, method and kit for enhancing human hair includingeyelashes.

BACKGROUND

Certain therapeutic agents have been known to induce hair growth. Oneexample is Minoxidil, 6-(1-piferidinyl)-2,4-pyrimidane-diamine 3-oxide(U.S. Pat. Nos. 3,382,247 and 3,644,363). Minoxidil was originallyprepared and sold for use as an antihypertensive. It was observed that,associated with the use of Minoxidil for this latter purpose, Minoxidiluse also produced an increase in hair growth and thickness as reportedin U.S. Pat. Nos. 4,139,619 and 4,968,812. Today, Minoxidil is marketedunder the trademark Rogaine® by Pfizer for the treatment of baldness onthe scalp for men (alopecia androgenetica) and women. Another example isfinasteride (Propecia®), marketed by Merck & Co. Finasteride wasoriginally developed for benign prostatic hypertrophy, and was found tobe effective in the treatment of alopecia androgenetica as reported inU.S. Pat. No. 4,968,812.

Among the drugs introduced for lowering intraocular pressure aremolecules of the family prostaglandin F2. The Upjohn Company identifieda prostaglandin F2α a analog, commonly known as Latanoprost and whosechemical name is isopropyl-(Z)-7[(1R, 2R, 3R,5S)3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylp-entyl]cyclopentyl]-5-heptenoate.Latanoprost is marketed by Pharmacia & Upjohn (currently a part ofPfizer) under the trademark Xalatan® for the reduction of elevatedintraocular pressure in patients with glaucoma and ocular hypertension.The form is a Latanoprost optical solution of 0.005% (50 μg/ml), and isapplied by dropper directly onto the eye. One drop generally containsapproximately 1.5 μg of Latanoprost.

In the course of its use for reduction of intraocular pressure,Latanoprost has been reported to cause, in some patients, an increasingpigmentation and growth of eyelashes. U.S. Pat. No. 6,262,105 statedthat the use of Latanoprost leads to increased length of lashes,increased numbers of lashes along the normal lash line, increasedthickness and luster of lashes, increased auxiliary lash-like terminalhair in transitional areas adjacent to areas of normal lash growth,increased lash-like terminal hairs at the medial and lateral canthalarea, increased pigmentation of the lashes, increased numbers, increasedlength, as well as increased luster, and thickness of fine hair on theskin of the adjacent lid, and increased perpendicular angulation oflashes and lash-like terminal hairs.

Alcon, Inc. (“Alcon”) introduced a prostaglandin F2α analog, commonlyknown as Travoprost whose chemical name is isopropyl (z)-7-[(1R, 2R, 3R,5S)-3,5-dihydroxy-2-[(1E,3R)-3-hydroxy-4-[(α,α,α-trifluoro-m-tolyl)oxyl]-1-butenyl]cyclopentyl]-5-heptenoateas a glaucoma treatment. Alcon also sought patent protection forTravoprost for growing hair in U.S. Patent Application No. 2003/0199590.

Allergan, Inc. (“Allergan”) introduced Bimatoprost whose chemical nameis cyclopentane N-ethylhaptanamide-5-cis-2-(3α-hydrosy-5-phenyl-1-trans-pentenyl)-3,5-dihydroxy,[1α,2α, 3α, 5α) for treating glaucoma. U.S. Pat. No. 7,351,404 is directedat the use of this molecule and similar molecules for growing hair,including eyelashes. Allergan distinguishes the Bimatoprost moleculefrom other prostaglandins on the basis that Bimatoprost is a prostamide.

U.S. Pat. Nos. 5,886,035 and 5,985,920 describe fluorine containingprostaglandin derivatives for use as a preventive or therapeuticmedicine for an eye disease such as glaucoma or elevated intraocularpressure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a process flow from a Corey acetate derivative to adifluoro compound that includes an ethyl amide.

DETAILED DESCRIPTION

Compositions for topical application, methods of topical application ofa composition to enhance hair, and a kit are described. Enhancing hairas used herein includes stimulating or promoting growth of existinghair, including stimulating or promoting a bulb or cells in a follicleassociated with the formation of an actual hair into hair growth. Hairgrowth in this sense includes an increase in length and/or an increasein diameter of a hair. Enhancing hair also includes conditioning hairand/or cosmetically improving the appearance or beauty of the hair suchthat hair subject to the compound or a composition including thecompound appears or feels longer, thicker and fuller. Enhancing hairalso includes darkening the hair. The location of the hair includes thescalp (e.g., scalp hair), eyelid (e.g., eyelashes), and brow (e.g.,eyebrows) and any other portion of human skin where hair exists or maybe desired.

In one embodiment, a composition includes an effective hair enhancingamount of a compound represented by the following formula:

wherein the dashed bonds represent a single or double bond that can bein the cis or trans configuration; R and R′ are individually selectedfrom hydrogen, or a C₁-C₆ straight or branched chain alkyl (e.g.,methyl, ethyl, isopropyl); X is a halide (e.g., F, Cl, Br, I) ahalide-containing group (e.g., CF₃), or hydrogen; either y=0 and x=1 ory=1 and x=0. The molecule may be characterized as a difluoroprostaglandin or prostaglandin-like compound because its backboneresembles a prostaglandin.

A difluoro compound may be in a molecular free form (a molecule) or anacceptable salt thereof (a compound). An acceptable salt is adermatologically acceptable salt or a pharmaceutically acceptable salt.An example of a salt is a hydrohalide salt of the molecule such as ahydrochloride salt. In one embodiment, the resulting salt compound willhave the proton from the hydrohalide bonded to the nitrogen of themolecule and be charge balanced by the halide. Throughout thisdescription, unless specifically indicated a reference to a compoundincludes a molecule or a compound.

In another embodiment, the compound has the following formula:

wherein R, R′, X, y and x are defined above, or an acceptable saltthereof.

In a particular embodiment, the compound is one of the followingmolecules or a salt thereof:

In one embodiment, one or more compounds described above is/are mixedwith a dermatologically compatible vehicle or carrier to form acomposition. Suitable vehicles include, for example, aqueous solutionssuch as e.g., physiological salines, oil (e.g., castor oil), solutions,foams, creams or ointments. Suitable vehicles furthermore may containdermatologically compatible preservatives such as e.g., benzalkoniumchloride, surfactants like e.g., polysorbate 80, liposomes or polymers,for example, methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidoneand hyaluronic acid; these may be used for increasing the viscosity.

In one embodiment, dermatological compositions for topical treatment forenhancing hair that include an effective hair enhancing amount of one ormore compounds as defined above and a dermatologically compatiblecarrier are also disclosed. Effective amounts of the active compoundsmay be determined by one of ordinary skill in the art but will varydepending on the compound employed, frequency of application and desiredresult. An amount of a compound or compounds will generally range fromabout 0.0000001 to about 10 percent, by weight, of the dermatologicalcomposition, preferably from about 0.0001 to about 10 percent, byweight, of total dermatological composition.

In another embodiment, a composition may include a combination ofdifluoro prostaglandin or prostaglandin-like compounds described or acompound(s) and other hair treatment aids such as an antioxidant (e.g.,Vitamin E), a vasodilator (e.g., minoxidil), an antimicrobial (e.g.,benzoyl peroxide), or an anti-inflammatory (e.g., hydrocortisone,cyclooxygenase inhibitor, lipooxigenase inhibitor).

The composition may be topically applied to the dermis of, for example,a human in an area desired for enhancing hair such as direct applicationto existing hair or the dermis in an area desired for hair enhancing asopposed to an indirect application such as to the surface of the eye.Such location may include the scalp, eyelash area or eyelid or brow of amale or female. Application of the compound(s) or composition to a baseof a hair or hairs may create a wicking action where the compound(s) aredrawn up the length of the hair or hairs. Repeated application for asustained period of time (e.g., daily for several weeks or more (e.g.,one month to several months)) may be desired.

Where hair is not present, the composition may be applied directly tothe dermis where hair growth is desired. This may include the scalpwhere, for example, a density of existing hair has been reduced due toalopecia or other mechanism (e.g., hair loss as a side effect tochemotherapy treatment). In certain Asian cultures, an absence of pubichair is considered bad luck and can be a serious problem, particularlyin women. The composition may be applied to the pubic area to addressthis problem. In one embodiment, repeated daily topical application of acomposition to an area of the dermis where hair growth is desired maycontinue until hair growth is effected and may continue periodically(daily, weekly) to maintain such growth. In one embodiment, such topicalapplication to the dermis may, for example, utilize a delivery vehicleincluding the composition that is a foam or cream.

To enhance eyelashes, a composition including at least one difluoroprostaglandin or prostaglandin-like compound as described above may beapplied at the base of an eyelid adjacent to or where hair grows fromthe follicles (e.g., along the lash line). Alternatively oradditionally, the composition may be applied to the eyelashesthemselves. Repeated application for consecutive days, weeks or months(e.g., regular daily application for six months) of the composition toeyelashes or areas of eyelid dermis associated with eyelashes (e.g., thebase of an eyelid containing follicles in which eyelashes grow) willcondition and cosmetically enhance existing eyelashes such that theeyelashes appear longer, thicker and fuller. Such application will alsostimulate or promote the growth of eyelashes.

In another embodiment, a kit is disclosed. The kit may include thecomposition of at least one difluoro prostaglandin or prostaglandin-likecompound as described above in a dermatologically compatible vehicle orcarrier in a container. The container includes an amount of thecomposition for repeated application over a period, such as enough ofthe composition for daily application over a period of six months. Thecontainer may also include an applicator, such as a mascara brush orother instrument for application of the composition to skin. In the caseof a composition in the form of a foam, the container may be pressurizedand include a nozzle to dispense a desired amount onto the hand of auser.

EXAMPLE 1 Synthesis of3,3-difluoro-4-phenoxybut-l-enyl-3,5-dihydroxycyclopentyl-hept-5-enoicacid

Starting from a Corey acetate derivative, an omega chain backbone, suchas dimethyl 2-oxo-3-phenoxy-propyl phosphonate is added via an exchangereaction. The oxo group in the 2 position is preserved in the formedintermediate and then reduced with a fluorine compound to produce adifluoro precursor. Subsequently, the alpha chain is added at anothersite of the Corey acetate derivative yielding3,3-difluoro-4-phenoxybut-1-enyl-3,5 -dihydroxycyclopentyl-hept-5-enoicacid.

EXAMPLE 2 Synthesis of3,3-difluoro-4-phenoxybut-l-enyl-3,5-dihydroxycyclopentyl-menthylhept-5-enoate

To the 3,3-difluoro-4-phenoxybut-1-enyl-3,5-dihydroxycyclopentyl-hept-5-enoic acidis added iodomethane in a solution of tetrahydroturan (THF) to form3,3-difluoro-4-phenoxybut-1-enyl-3,5-dihydroxycyclopentyl-methylhept-5-enoate.

EXAMPLE 3 Synthesis of3,3-difluoro-4-phenoxybut-l-enyl-3,5-dihydroxycyclopentyl-N-ethylhept-5-enamide

To the3,3-difluoro-4-phenoxybut-l-enyl-3,5-dihydroxycyclopentyl-methylhept-5-enoateis added ethylamine in water to form3,3-difluoro-4-phenoxybut-1-enyl-3,5-dihydroxycyclopentyl-N-ethylhept-5-enamide.

FIG. 1 shows a process flow from a Corey acetate derivative to the acid,to the ester and then to an ethyl amide (Compound 3). U.S. Pat. No.5,886,035 also describes a method of preparing difluoro-prostaglandinderivatives but does not describe the use of such derivatives in hair(eyelash) growth.

The following examples provide representative compositions including adifluoro compound such as Compound 3:

EXAMPLE 4 Eyelash Composition

Ingredient Percentage  1. Water (Aqua) 97.791  2. Sodium Chloride 0.877 3. Panthenol 0.020  4. Citric Acid 0.030  5. Phenoxyethanol 0.300  6.Chlohenesin 0.300  7. Disodium Phosphate 0.142  8. Difluoro Compound0.024  9. Alcohol 0.216 10. Cellulose Gum 0.300

EXAMPLE 5 Eyelash Composition

Ingredient Percentage  1. USP Water 94.519  2. Sodium Chloride 0.077  3.Phosphoric Acid 0.03  4. Phenoxyethanol 0.3  5. Chlorphenesin 0.3  6.Disodium Phosphate 0.142  7. Cellulose Gum 0.36  8. Biotin 0.5  9.Glycerin 0.6 10. Swertia Japonica Extract 0.045 11. Saw Palmetto Extract0.064 12. Camellia Sinensis (White 0.054   Tea) Leaf Extract 13. PanaxGinseng 0.075 14. Octapeptide-2 0.93 15. Biotinoyl Tripeptide-1 0.93 16.Wheat Protein 0.25 17. Calendula 0.8 18. Difluoro Compound 0.024

EXAMPLE 6 Eyelash Composition

Ingredient Percentage  1. USP Water 96.031  2. Actiphyte of Rosemary0.025  3. Phosphoric Acid 0.001  4. Phenoxyethanol 0.3  5. Chlorphenesin0.3  6. Disodium Phosphate 0.985  7. Cellulose Gum 0.36  8. Biotin 0.24 9. Panthenol 0.25 10. Actiphyte of Nettles 0.1 11. Actiphyte ofHorsetail 0.098 12. Actiphyte of Psoralea Seed 0.15 13. Mulberry RootExtract 0.07 14. Actiphyte of Japanese Green Tea 0.25 15. Glycerin 0.616. Difluoro Compound (in 10% 0.24   Ethanol Solution)

EXAMPLE 7 Scalp Composition

Ingredient Percentage  1. Water 95.00000  2. Acrylates Copolymer 1.50000  3. Glycerin  1.00000  4. Phenoxyethanol  0.80000  5. SodiumCocoyl Glutamate  0.35000  6. Chlorphenesin  0.30000  7. Polysorbate 0.25000  8. Trifluoromethyl Dechloro  0.24000   Ethylprostenolamide  9.Disodium EDTA 0.10000 10. Fragrance 0.09610 11. Aminomethyl Propanol0.09000 12. Panax Ginseng Root Extract 0.08000 13. Panthenol 0.08000 14.Ginko Bilola Leaf Extract 0.05000 15. Biotin 0.05000 16. SerenoaSerrulata Fruit Extract 0.00640 17. Swertia Japonica Extract 0.00450 18.Hydrolyzed Wheat Protein 0.00300

In another embodiment, compositions for topical application and methodsof topical application of a composition to modify hair are describedwherein the modification includes increased curl of hair on a subject orhair that is not biologically attached to or is not naturally a part ofa subject (e.g., hair of a wig or extension) (“non-natural hair”). Inanother embodiment, the modification includes increased curl of the hairtogether with conditioning hair and/or cosmetically improving theappearance or beauty of the hair (e.g., increased look and feel ofsoftness and silkiness). Thus, the compositions described may be appliedto existing hair on the scalp or eyelashes or non-natural hair toincrease the curl and/or the look and feel of the hair. In oneembodiment, a composition includes an effective amount of a compoundrepresented by the following formula:

wherein the dashed bonds represent a single or double bond and when abond in either chain is a double bond, cis or trans configuration iscontemplated;

wherein A and B are individually selected from a hydrogen atom, ahydroxyl group (—OH) and a halogen atom (e.g., a fluorine atom), withthe proviso that when one of A and B is a hydroxyl group, the other of Aand B is a hydrogen atom and when one of A and B is a halogen atom, theother of A and B is a halogen atom or a hydrogen atom;

wherein Z is a cycloalkyl moiety having from three to seven carbonatoms, an aryl moiety including from four to ten carbon atoms or aheteroaryl moiety including three to nine carbon atoms and at least oneheteroatom selected from nitrogen, oxygen and sulfur; and

wherein X₁ and X₂ are individually selected from a hydrogen atom, analkyl moiety having from one to six carbon atoms,

and

R⁵ is an alkyl moiety having from one to six carbon atoms;

wherein R₁ and R₂ are individually selected from an oxo group (=O), ahydroxyl group (—OH) or an ester group (—O(CO)R₆), and R₆ is a saturatedor unsaturated acyclic hydrocarbon group having from 1 to about 20carbon atoms, and —(CH₂)_(m)R₇ wherein m is 0 or an integer of from 1 to10, and R₇ is cycloalkyl group, having from three to seven carbon atoms,or an aryl or heteroaryl group, as defined above;

wherein y is 0 or 1, x is 0 or 1 and x and y are not both 1.

The compound may be in free form (a molecule) or an acceptable saltthereof (a compound) such as a cationic or anionic salt formed at thenitrogen atom of the molecule, in association with a carrier adapted fortopical application to mammalian skin. Unless specified, reference to acompound will include a molecule or a compound.

In one embodiment, the compound is represented by the following formula:

wherein Y is selected from an alkyl group, a halogen atom (e.g.,fluorine, chlorine), a nitro group, an amino group, a thiol group, ahydroxy group, an alkyloxy group, an alkylcarboxy group, a halosubstituted alkyl wherein the alkyl includes from one to six carbonatoms, and n is 0 or an integer of from 1 to 3, or an acceptable saltthereof.

In another embodiment, the compound has the following formula:

wherein A, B, X₁, X₂, Y and n are as defined above, or an acceptablesalt thereof.

In a particular embodiment, the compound is selected from any ofcompounds (1)-(5) above or a molecule having one of the followingformulas or a salt thereof:

Compounds (6)-(9) may be prepared using techniques known in the artincluding, for example, techniques described in U.S. Pat. Nos.5,001,153; 5,422,368; 5,510,383; and 5,607,978.

In one embodiment, the one or more compounds described above (includingcompounds (1)-(9) is/are mixed with a dermatologically compatiblevehicle or carrier. Suitable vehicles include, for example, aqueoussolutions such as e.g., physiological salines, oil (e.g., castor oil),water solutions, water/alcohol solutions or ointments. Suitable vehiclesfurthermore may contain dermatologically compatible preservatives suchas e.g., benzalkonium chloride, surfactants like e.g., polysorbate 80,liposomes or polymers, for example, methyl cellulose, polyvinyl alcohol,polyvinyl pyrrolidone and hyaluronic acid; these may be used forincreasing the viscosity.

In one embodiment, dermatological compositions for topical treatment forinducing or stimulating modification of existing hair includingincreased curl which include an effective hair modifying amount of oneor more compounds as defined above and a dermatologically compatiblecarrier are also disclosed wherein the modification includes increasedcurl of hair or increased curl. Effective amounts of the compound may bedetermined by one of ordinary skill in the art but will vary dependingon the compound employed, frequency of application and desired result,and the compound will generally range from about 0.0000001 to about 50%,by weight, of the dermatological composition, preferably from about0.001 to about 50%, by weight, of total dermatological composition, morepreferably from about 0.1 to about 30%, by weight of the composition. Inanother embodiment, a composition may include a combination of compoundsdescribed or a compound(s) and other hair treatment aids such as anantioxidant (e.g., Vitamin E), a vasodilator (e.g., minoxidil), anantimicrobial (e.g., benzoyl peroxide), or an anti-inflammatory (e.g.,hydrocortisone, cyclooxygenase inhibitor, lipooxigenase inhibitor).

The composition may be topically applied to existing hair and retainedon the hair. Such location may include the scalp or eyelash area of amale or female. Repeated application for a sustained period of time(e.g., daily for several weeks or more (e.g., one month to severalmonths)) may be desired. The composition may be beneficial to personsthat naturally have straight scalp hair to aid in the curl of such hair.Evidence of the effectiveness of a composition of compound (3)(dechloro-dihydroxy-difluoro-ethylcloprostenate) and, alternatively, ofcompound (8) (trifluoromethyl dechloroethyl prostenolamide) inapplication to generally straight Asian hair indicates a profoundcurling effect.

In one embodiment, the composition is suitable for modifying eyelashes.To modify eyelashes, a composition would be provided to a subject withinstructions on use (e.g., by instructions on or with a kit, the kitincluding the composition and the instructions). The subject would beinstructed to apply the composition to eyelash hair. In addition tomodifying the eyelashes (e.g., increasing the curl and/or look andfeel), it is anticipated that application to a hair follicle willincrease the thickness (e.g., diameter) of the follicle.

In one embodiment, the composition may be topically applied to hair onthe scalp. For example, a subject interested in establishing a curl to aportion of the subject's scalp hair or improving a natural curl, wouldbe instructed (e.g., by instructions on or with a kit) to topicallyapply the composition to the desired portion of the hair and to leavethe composition on the hair. To improve or sustain the curl over aperiod of time (e.g., days, weeks), the subject would be instructed torepeat the application for a period ranging from days to weeks.

In another embodiment, the applications described above may be used tomodify non-natural hair (e.g., hair not biologically attached to or isnot naturally a part of a subject). Examples of such hair include, butare not limited to, wigs and hair extensions.

In another embodiment, a kit is disclosed. The kit may include thecomposition of at least one compound having the formula III or IV asdescribed above in a dermatologically compatible vehicle or carrier in acontainer. The container includes an amount of the composition forrepeated application over a period, such as enough of the compositionfor daily application over a period of six months. The container mayalso include an applicator, such as a mascara brush or other instrumentfor application of the composition to skin. In the case of a compositionin the form of a foam, the container may be pressurized and include anozzle to dispense a desired amount onto the hand of a user.

EXAMPLE

The following example used trifluoromethyl dechloroethyl prostenolamide(TDP) as a compound. TDP has the following formula:

A solution of TDP was prepared including 97.6 percent water, 0.24percent TDP and 2.16 percent ethyl alcohol. Samples of human hairseparated from a subject were treated with water alone while others weretreated with the TDP solution. The treatment involved dipping the dryhair samples into the water and TDP solutions to one minute.Unexpectedly, there appeared a definite increase in curl in each of thehair samples when treated with the TDP solution. The hair treated withwater alone did not show similar curl. The results are illustrated inFIG. 1. In addition, the hair treated with the TDP solution had anoticeable and palpable increase in the look and feel of softness andsilkiness compared to the hair treated with the water alone.

In the preceding detailed description, reference is made to specificembodiments thereof. It will, however, be evident that variousmodifications and changes may be made thereto without departing from thebroader spirit and scope of the following claims. The specification anddrawings are, accordingly, to be regarded in an illustrative rather thana restrictive sense.

What is claimed is:
 1. A composition comprising a compound of the formula:

wherein the dashed bonds represent a single or double bond; R and R′ are individually selected from the group consisting of hydrogen, a C₁-C₆ straight or branched chain alkyl; X is selected from the group consisting of a halide, a halide containing group or a hydrogen; y is 0 or 1, x is 0 or 1 and x and y are not both 1 or not both 0; or a salt thereof.
 2. A composition of claim 1, wherein the compound has the formula:


3. A composition of claim 2, wherein the compound has the formula:


4. A composition of claim 2, wherein the compound has the formula:


5. A composition of claim 2, wherein the compound has the formula:


6. A composition of claim 2, wherein the compound has the formula:


7. The composition of claim 1, further comprising a dermatologically acceptable carrier.
 8. A method comprising: directly applying to dermis or hair on the dermis an amount of a composition comprising a compound of the formula:

wherein the dashed bonds represent a single or double bond, R and R′ are individually selected from the group consisting of hydrogen, a C₁-C₆ straight or branched chain alkyl, X is selected from the group consisting of a halide, a halide containing group or a hydrogen, y is 0 or 1, x is 0 or 1 and x and y are not both 1, or a salt thereof.
 9. The method of claim 7, wherein the dermis includes an eyelid.
 10. The method of claim 8, wherein the compound has the formula:


11. The method of claim 8, wherein the compound has the formula:


12. The method of claim 8, wherein the compound has the formula:


13. The method of claim 8, wherein the compound has the formula:


14. The method of claim 8, wherein the composition further comprises a dermatologically acceptable carrier.
 15. A kit comprising: a container; a composition comprising a compound of the formula:

wherein the dashed bonds represent a single or double bond; R and R′ are individually selected from the group consisting of hydrogen, a C₁-C₆ straight or branched chain alkyl; X is selected from the group consisting of a halide, a halide containing group or a hydrogen; y is 0 or 1, x is 0 or 1 and x and y are not both 1 or not both 0; or a pharmaceutically acceptable salt thereof, and wherein the container includes an amount of the composition for repeated application over a period.
 16. The kit of claim 15 further comprising an applicator.
 17. The kit of claim 15, wherein the compound is selected from at least one of the following: 